chr1-150577397-C-T

Variant names:

• chr1-150577397-C-T
• ENST00000307940.3:c.783G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182763.3(MCL1):​c.783G>A​(p.Trp261*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCL1 NM_182763.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11

Genes affected

MCL1 (HGNC:6943): (MCL1 apoptosis regulator, BCL2 family member) This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCL1	NM_021960.5	c.1031G>A	p.Gly344Asp	missense_variant	Exon 3 of 3	ENST00000369026.3	NP_068779.1
MCL1	NM_182763.3	c.783G>A	p.Trp261*	stop_gained	Exon 2 of 2		NP_877495.1
MCL1	NM_001197320.2	c.572G>A	p.Gly191Asp	missense_variant	Exon 4 of 4		NP_001184249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCL1	ENST00000369026.3	c.1031G>A	p.Gly344Asp	missense_variant	Exon 3 of 3	1	NM_021960.5	ENSP00000358022.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;D
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.1	.;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.055	T;D
Polyphen		1.0	.;D
Vest4		0.57
MutPred		0.41		.;Loss of catalytic residue at G342 (P = 0.1222);
MVP		0.56
MPC		1.7
ClinPred		0.94	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150549873;